The overall goal of this University of Texas MD Anderson Cancer Center SPORE in Genitourinary Cancer is to facilitate innovative translational research in the prevention, detection, and treatment of this disease leading to the elimination of bladder cancer (BC) as a major health problem. We have invested in several major translational research themes which include: the development of non- or minimally-invasive markers for early detection of BC in high-risk individuals or for surveillance and the early detection of recurrence in those with the disease, the identification of inherited factors that contribute to increased or decreased risk of developing BC, the elucidation of the molecular events (genetic and epigenetic) that mediate the earliest stages of urothelial neoplasia, the determination of whether activating mutations and gene amplifications present in BCs drive cancer progression and serve as potential therapeutic targets, the identification of molecular and biological markers that can be used to distinguish favorable from unfavorable biology in non-muscle Invasive and more advanced disease that direct us to optimal therapy (personalized medicine), the development of novel therapeutic approaches for non-muscle Invasive BC that are alternatives to bacillus Calmette-Guerin (BCG) and/or are effective in BCG-refractory disease, and the Identification of novel agents for the treatment of metastatic BC. To achieve these goals, our SPORE has assembled clinicians and basic scientists including urologists, medical oncologists, pathologists, molecular epidemiologists, molecular and cell biologists, biostatisticians, and experts in development of new technologies and informatics. The SPORE includes 5 inter-related projects that deal with 1) early detection of BC, 2) risk assessment for BC 3) biology and therapeutic targeting of the fibroblast growth factor receptor -3, 4) therapeutic targeting of Ral GTPases, and 5.) the development of adenoviral mediated gene therapy for refractory tumors. These projects are supported by 3 Cores: (A) Administrative; (B). Biostatistics and Bioinformatics; and (C) Pathology & Data Management. All of the scientific projects are translational in nature; focus on human BC; involve clinical and basic investigators and biostatisticians; interact with the other projects; and utilize Core resources. Innovative Developmental and Career Development Projects have brought new investigators into and stimulated the SPORE that are represented in each of the major projects. Achievement of the aims and objectives of this proposal will result in a major decrease in the incidence, morbidity and mortality of BC.